Intravenous Administration Is an Effective and Safe Route for Cancer Gene Therapy Using the Bifidobacterium-Mediated Recombinant HSV-1 Thymidine Kinase and GanciclovirReportar como inadecuado




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Molecular Medicine and Cancer Research Center, Department of Biochemistry and Molecular Biology, Chongqing Medical University, Yuzhong District, Yi XueYuan Road, Number 1, Chongqing 400016, China



These authors contributed equally to this work.





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Academic Editor: Ge Zhang

Abstract The herpes simplex virus thymidine kinase-ganciclovir HSV TK-GCV system is one of the best studied cancer suicide gene therapy systems. Our previous study showed that caspase 3 expression was upregulated and bladder tumor growth was significantly reduced in rats treated with a combination of Bifidobacterium BF and HSV TK-GCV BF-rTK-GCV. However, it was raised whether the BF-mediated recombinant thymidine kinase combined with ganciclovir BF-rTK-GCV was safe to administer via venous for cancer gene therapy. To answer this question, the antitumor effects of BF-rTK-GCV were mainly evaluated in a xenograft nude mouse model bearing MKN-45 gastric tumor cells. The immune response, including analysis of cytokine profiles, was analyzed to evaluate the safety of intramuscular and intravenous injection of BF-rTK in BALB-c mice. The results suggested that gastric tumor growth was significantly inhibited in vivo by BF-rTK-GCV. However, the BF-rTK-GCV had no effect on mouse body weight, indicating that the treatment was safe for the host. The results of cytokine profile analysis indicated that intravenous injection of a low dose of BF-rTK resulted in a weaker cytokine response than that obtained with intramuscular injection. Furthermore, immunohistochemical analysis showed that intravenous administration did not affect the expression of immune-associated TLR2 and TLR4. Finally, the BF-rTK-GCV inhibited vascular endothelial growth factor VEGF expression in mouse model, which is helpful for inhibiting of tumor angiogenesis. That meant intravenous administration of BF-rTK-GCV was an effective and safe way for cancer gene therapy. View Full-Text

Keywords: cancer; gene therapy; Bifidobacterium; safety; thymidine kinase; ganciclovir; vascular endothelial growth factor VEGF cancer; gene therapy; Bifidobacterium; safety; thymidine kinase; ganciclovir; vascular endothelial growth factor VEGF





Autor: Huicong Zhou †, Zhiliang He †, Changdong Wang, Tingting Xie, Lin Liu, Chuanyang Liu, Fangzhou Song and Yongping Ma *

Fuente: http://mdpi.com/



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